P2RX1

Official Full Name

purinergic receptor P2X 1

Organism

Homo sapiens

GeneID

5023

Background

The protein encoded by this gene belongs to the P2X family of G-protein-coupled receptors. These proteins can form homo-and heterotimers and function as ATP-gated ion channels and mediate rapid and selective permeability to cations. This protein is primarily localized to smooth muscle where binds ATP and mediates synaptic transmission between neurons and from neurons to smooth muscle and may being responsible for sympathetic vasoconstriction in small arteries, arterioles and vas deferens. Mouse studies suggest that this receptor is essential for normal male reproductive function. This protein may also be involved in promoting apoptosis. [provided by RefSeq, Jun 2013]

Synonyms

P2X1;

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Detailed Information

Purinergic receptors use multiple extracellular nucleotides (especially ATP) and their ultimate degradation product adenosine (ADO) as transport molecules and are critical for regulating a variety of cellular functions, including death, growth autophagy, and metabolism. Purinergic receptors can be divided into seven P2RXs (P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX6, and P2RX7), eight P2RYs (P2RY1, P2RY2, P2RY4, P2RY6, P2RY11, P2RY12, P2RY13, and P2RY14), and four P1 receptors (ADORA1, ADORA2A, ADORA2B, ADORA3). Extracellular purine is a necessary factor for regulating immune cell transport and immunophenotype. Purinergic receptor P2RX1 plays important role in multiple physiological processes, including smooth muscle contraction and immunity, renal ischemia, and pancreatic cancer immune evasion.

P2RX1 Associated With Pancreatic Cancer

Pancreatic duct adenocarcinoma (PDAC), as one of the most lethal malignant tumors in human beings, is harmful due to its high metastatic potential. The occurrence of tumor immune escape and tumor growth depends on the immunosuppressive microenvironment. Recently, neutrophils were demonstrated to be a vital immune component of tumor microenvironment for PDAC liver metastatic by Wang et al. Specifically, it is demonstrated that tumors escape antitumor immunity through the accumulation of a variety of purinergic receptor (P2RX1)-negative neutrophils. The immune and metabolic phenotypes of P2RX1-negative neutrophils from P2XR1 knockout mice were compared with the neutrophils from wild-type mice based on various experiments, including RNA sequencing, cell fluorescence analysis, and metabolic analysis. As the result showed, the level of immunosuppressive molecules has been significantly increased by P2RX1-negative neutrophils. Furthermore, the up-regulation of transcription factor erythroid 2-related factor 2 (NRF2) has been observed in P2RX1 deficient neutrophils and NRF2 is related to the expression and metabolic reorganization of programmed death-ligand 1 (PD-L1).

P2RX1 Associated With Alleviating Renal Ischemia

Renal ischemia-reperfusion injury (IRI), as one of the most common reasons for causing acute renal injury (AKI), continues to bring great challenges to clinical transplantation. Despite the significant progress that has been achieved in clinical and laboratory research, the incidence rate and mortality of renal IRI are still high based on epidemiological studies. Therefore, it is still urgent to further study the pathophysiological mechanism of IRI and explore new therapeutic targets. The expression pattern of the purinergic receptor was screened based on RNA sequencing by Zhuang et al., they found that the expression of P2RX1 has significantly increased in IR injured kidney. They also found that fully renal IRI was fully attenuated and mitochondrial dynamics was restored due to P2RX1 deletion, which is demonstrated by using P2RX1 knockout mice. Further mechanical studies proved that the metabolic interaction participated by P2RX1 promoted the formation of NETs, and then destroyed the mitochondrial dynamics in renal IRI.

P2RX1 Associated With Alleviating Inflammation in Colitis

Inflammatory bowel disease (IBD) is still one of the most common gastrointestinal diseases in the world. Purinergic signal transduction has become a promising therapeutic target for inflammation-related diseases. However, the specific role of purinergic receptors in IBD is unclear. Wang et al. screened the expression profile of purinergic receptors in the published GEO (Gene Expression Omnibus) data set, and the significantly up-regulated expression of P2RX1 was found in inflammatory colon tissue. It is shown by the RNA sequencing of colon tissue that P2RX1 gene knockout could inhibit the inflammatory response of DSS-induced colitis in mice. Their study suggests that P2RX1 as a targeting purinergic receptor may provide a new strategy for the treatment of IBD.

P2RX1 Figure 1. the schematic illustration of the circularization of P2RX1 (Gao et al., 2020).

References:

Gao Y, Liu J, Huan J, et al. Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7. Cancer Cell International, 2020, 20(1): 1-13.
Zhuang S, Xia S, Huang P, et al. Targeting P2RX1 alleviates renal ischemia/reperfusion injury by preserving mitochondrial dynamics. Pharmacological Research, 2021: 105712.
Wang X, Yuan X, Su Y, et al. Targeting Purinergic Receptor P2RX1 Modulates Intestinal Microbiota and Alleviates Inflammation in Colitis. Frontiers in immunology, 2021, 12.

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